Promoter architecture and the evolvability of gene expression

Evolutionary changes in gene expression are a main driver of phenotypic evolution. In yeast, genes that have rapidly diverged in expression are associated with particular promoter features, including the presence of a TATA box, a nucleosome-covered promoter and unstable tracts of tandem repeats. Here, we discuss how these promoter properties may confer an inherent capacity for flexibility of expression

Development of intuitive rules: Evaluating the application of the dual-system framework to understanding children's intuitive reasoning

This is an author-created version of this article. The original source of publication is Psychon Bull Rev. 2006 Dec;13(6):935-53 The final publication is available at www.springerlink.com Published version: http://dx.doi.org/10.3758/BF0321390

Does surgeon sex and anthropometry matter for tool usability in traditional laparoscopic surgery? A systematic review and meta-analysis

Copyright © The Author(s) 2023 Introduction: Hand size, strength, and stature all impact a surgeon’s ability to perform Traditional Laparoscopic Surgery (TLS) comfortably and effectively. This is due to limitations in instrument and operating room design. This article aims to review performance, pain, and tool usability data based on biological sex and anthropometry. Methods: PubMed, Embase, and Cochrane databases were searched in May 2023. Retrieved articles were screened based on whether a full-text, English article was available in which original results were stratified by biological sex or physical proportions. Article quality was discussed using the Mixed Methods Appraisal Tool (MMAT). Data were summarized in three main themes: task performance, physical discomfort, and tool usability and fit. Task completion times, pain prevalence, and grip style results between male and female surgeons formed three meta-analyses. Results: A total of 1354 articles were sourced, and 54 were deemed suitable for inclusion. The collated results showed that female participants, predominantly novices, took 2.6–30.1 s longer to perform standardized laparoscopic tasks. Female surgeons reported pain at double the frequency of their male colleagues. Female surgeons and those with a smaller glove size were consistently more likely to report difficulty and require modified (potentially suboptimal) grip techniques with standard laparoscopic tools. Conclusions: The pain and stress reported by female or small-handed surgeons when using laparoscopic tools demonstrates the need for currently available instrument handles, including robotic hand controls, to become more size-inclusive. However, this study is limited by reporting bias and inconsistencies; furthermore, most data was collected in a simulated environment. Additional research into how anthropometric tool design impacts the live operating performance of experienced female surgeons would further inform this area of investigation.Open Access funding enabled and organized by CAUL and its Member Institutions. This review was commissioned and funded by CMR Surgical Ltd

Using resource graphs to represent conceptual change

We introduce resource graphs, a representation of linked ideas used when reasoning about specific contexts in physics. Our model is consistent with previous descriptions of resources and coordination classes. It can represent mesoscopic scales that are neither knowledge-in-pieces or large-scale concepts. We use resource graphs to describe several forms of conceptual change: incremental, cascade, wholesale, and dual construction. For each, we give evidence from the physics education research literature to show examples of each form of conceptual change. Where possible, we compare our representation to models used by other researchers. Building on our representation, we introduce a new form of conceptual change, differentiation, and suggest several experimental studies that would help understand the differences between reform-based curricula.Comment: 27 pages, 14 figures, no tables. Submitted for publication to the Physical Review Special Topics Physics Education Research on March 8, 200

The gene SMART study: method, study design, and preliminary findings

The gene SMART (genes and the Skeletal Muscle Adaptive Response to Training) Study aims to identify genetic variants that predict the response to both a single session of High-Intensity Interval Exercise (HIIE) and to four weeks of High-Intensity Interval Training (HIIT). While the training and testing centre is located at Victoria University, Melbourne, three other centres have been launched at Bond University, Queensland University of Technology, Australia, and the University of Brighton, UK. Currently 39 participants have already completed the study and the overall aim is to recruit 200 moderately-trained, healthy Caucasians participants (all males 18–45 y, BMI \u3c 30). Participants will undergo exercise testing and exercise training by an identical exercise program. Dietary habits will be assessed by questionnaire and dietitian consultation. Activity history is assessed by questionnaire and current activity level is assessed by an activity monitor. Skeletal muscle biopsies and blood samples will be collected before, immediately after and 3 h post HIIE, with the fourth resting biopsy and blood sample taken after four weeks of supervised HIIT (3 training sessions per week). Each session consists of eight to fourteen 2-min intervals performed at the pre-training lactate threshold (LT) power plus 40 to 70% of the difference between pre-training lactate threshold (LT) and peak aerobic power (Wpeak). A number of muscle and blood analyses will be performed, including (but not limited to) genotyping, mitochondrial respiration, transcriptomics, protein expression analyses, and enzyme activity. The participants serve as their own controls. Even though the gene SMART study is tightly controlled, our preliminary findings still indicate considerable individual variability in both performance (in-vivo) and muscle (in-situ) adaptations to similar training. More participants are required to allow us to better investigate potential underlying genetic and molecular mechanisms responsible for this individual variability

Renal Function Following Three Distinct Weight Loss Dietary Strategies During 2 Years of a Randomized Controlled Trial

OBJECTIVE This study addressed the long-term effect of various diets, particularly low-carbohydrate high-protein, on renal function on participants with or without type 2 diabetes. RESEARCH DESIGN AND METHODS In the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT), 318 participants (age, 51 years; 86% men; BMI, 31 kg/m2; mean estimated glomerular filtration rate [eGFR], 70.5 mL/min/1.73 m2; mean urine microalbumin-to-creatinine ratio, 12:12) with serum creatinine 0.05) across diet groups. The increased eGFR was at least as prominent in participants with (+6.7%) or without (+4.5%) type 2 diabetes or those with lower baseline renal function of eGFR <60 mL/min/1.73 m2 (+7.1%) versus eGFR ≥60 mL/min/1.73 m2 (+3.7%). In a multivariable model adjusted for age, sex, diet group, type 2 diabetes, use of ACE inhibitors, 2-year weight loss, and change in protein intake (confounders and univariate predictors), only a decrease in fasting insulin (β = −0.211; P = 0.004) and systolic blood pressure (β = −0.25; P < 0.001) were independently associated with increased eGFR. The urine microalbumin-to-creatinine ratio improved similarly across the diets, particularly among participants with baseline sex-adjusted microalbuminuria, with a mean change of −24.8 (P < 0.05). CONCLUSIONS A low-carbohydrate diet is as safe as Mediterranean or low-fat diets in preserving/improving renal function among moderately obese participants with or without type 2 diabetes, with baseline serum creatinine <176 μmol/L. Potential improvement is likely to be mediated by weight loss–induced improvements in insulin sensitivity and blood pressure

Cs⁺ incorporation into CH₃NH₃PbI₃ perovskite:substitution limit and stability enhancement

In this study we systematically explored the mixed cation perovskite Csx(CH3NH3)1−xPbI3.</p

Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma

Human cancers are complex ecosystems composed of cells with distinct phenotypes, genotypes, and epigenetic states, but current models do not adequately reflect tumor composition in patients. We used single-cell RNA sequencing (RNA-seq) to profile 430 cells from five primary glioblastomas, which we found to be inherently variable in their expression of diverse transcriptional programs related to oncogenic signaling, proliferation, complement/immune response, and hypoxia. We also observed a continuum of stemness-related expression states that enabled us to identify putative regulators of stemness in vivo. Finally, we show that established glioblastoma subtype classifiers are variably expressed across individual cells within a tumor and demonstrate the potential prognostic implications of such intratumoral heterogeneity. Thus, we reveal previously unappreciated heterogeneity in diverse regulatory programs central to glioblastoma biology, prognosis, and therapy.National Institutes of Health (U.S.) (U24 CA180922

Evolution of a Membrane Protein Regulon in Saccharomyces

Expression variation is widespread between species. The ability to distinguish regulatory change driven by natural selection from the consequences of neutral drift remains a major challenge in comparative genomics. In this work, we used observations of mRNA expression and promoter sequence to analyze signatures of selection on groups of functionally related genes in Saccharomycete yeasts. In a survey of gene regulons with expression divergence between Saccharomyces cerevisiae and S. paradoxus, we found that most were subject to variation in trans-regulatory factors that provided no evidence against a neutral model. However, we identified one regulon of membrane protein genes controlled by unlinked cis- and trans-acting determinants with coherent effects on gene expression, consistent with a history of directional, nonneutral evolution. For this membrane protein group, S. paradoxus alleles at regulatory loci were associated with elevated expression and altered stress responsiveness relative to other yeasts. In a phylogenetic comparison of promoter sequences of the membrane protein genes between species, the S. paradoxus lineage was distinguished by a short branch length, indicative of strong selective constraint. Likewise, sequence variants within the S. paradoxus population, but not across strains of other yeasts, were skewed toward low frequencies in promoters of genes in the membrane protein regulon, again reflecting strong purifying selection. Our results support a model in which a distinct expression program for the membrane protein genes in S. paradoxus has been preferentially maintained by negative selection as the result of an increased importance to organismal fitness. These findings illustrate the power of integrating expression- and sequence-based tests of natural selection in the study of evolutionary forces that underlie regulatory change